DESCRIPTION: Several lines of evidence indicate that Type 2 (non-insulin-dependent) diabetes mellitus is a heterogeneous disease that results from a combination of abnormalities in both insulin secretion and insulin action. The causes of decreased insulin secretion in Type 2 diabetes are still not completely understood, but in a subgroup of Type 2 diabetic patients they may be related to an autoimmune destruction of the pancreatic beta cells. A pronounced activation of the acute-phase response, that was found to be associated with islet cell autoimmunity in the Preliminary Studies, may in part explain the defect in insulin secretion seen in Type 2 diabetes. There have been no extensive investigations, particularly in the U.S., with regard to the prevalence and clinical significance of islet cell autoimmunity particularly in elderly patients with Type 2 diabetes. Two of the most widely used markers for the diagnosis and prediction of autoimmune diabetes, namely GAD65 and IA-2 autoantibodies, along with inflammatory markers of activation of the acute phase response, will be applied in a well-characterized population of Type 2 diabetic patients over the age of 65 from the Cardiovascular Health Study (CHS). The CHS is a longitudinal study, which was proposed to identify and evaluate factors, such as diabetes mellitus, related to the incidence and the natural history of Coronary Heart Disease (CHD) and stroke in non-institutionalized adults 65 years and older. The identification of individuals at risk of developing autoimmune Type 2 diabetes is of public health interest because immunomodulatory strategies could potentially be instituted early enough to prevent the complications related with hyperglycemia and, possibly, the time of onset of insulin requirement. A more appropriate characterization of a subgroup of Type 2 diabetic patients of autoimmune pathogenesis will be of benefit to future research into the etiology, natural history as well as treatment of Type 2 diabetes mellitus.